Assessment of sarcoplasmic reticulum Ca2+-uptake during the development of left ventricular hypertrophy


    loading  Checking for direct PDF access through Ovid

Abstract

Cardiac sarcoplasmic reticulum (SR) sequesters Ca2+ and plays a crucial role in the regulation of intracellular Ca2+. Its functional properties are central to the excitation-contraction cycle of cardiac muscle. In this study, we hypothesized that alterations in SR function occur during the development of left ventricular (LV) hypertrophy. LV hypertrophy was produced in Lewis rats by the one-kidney, one-clip (1K1C) procedure. LV tissues were obtained from 1K1C rats 1 week (mild, N=7), 4 weeks (moderate, N=7), and 8 weeks (severe, N=7) post-surgery and from the corresponding age-matched, sham-operated controls (N=7 at each stage). In all of these rats, the ratio of LV weight (g) to body weight (kg) was determined and considered as an index for LV hypertrophy. In addition, the ratio of lung weight (g) to body weight (kg) was determined and considered as an index for pulmonary congestion and heart failure. In each LV specimen, SR Ca2+-uptake and tissue Ca2+-ATPase (CAA) level were determined. In 1K1C rats, LV hypertrophy increased by 21, 40, and 90% at 1, 4, and 8 weeks post-surgery, respectively, compared to the age-matched, sham-operated rats, whereas pulmonary congestion did not occur at 1 and 4 weeks but increased significantly by about 21% at 8 weeks. Further, both SR Ca2+-uptake and immunodetectable CAA level did not change at 1 week, increased (54%) to the same extent at 4 weeks, and decreased (42%) by approximately the same extent at 8 weeks in 1K1C rats compared to the age-matched, sham-operated rats. In summary, as LV hypertrophy evolved, Ca2+-uptake and CAA expression did not change in the early, increased in the moderate, and then declined in the later stages of hypertrophy development. The increase in Ca2+-uptake and CAA expression suggests, at the cellular level, a compensatory response to LV hypertrophy, while the decline at later stages indicates the transition to heart failure.

    loading  Loading Related Articles